NM_001110792.2:c.*544G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001110792.2(MECP2):c.*544G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 148,289 control chromosomes in the GnomAD database, including 1 homozygotes. There are 90 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., 65 hem., cov: 23)

Exomes 𝑓: 0.0024 ( 0 hom. 25 hem. )

Consequence

MECP2
NM_001110792.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -1.07

Publications

0 publications found

Variant links:

Genes affected

MECP2 (HGNC:6990): (methyl-CpG binding protein 2) DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. In contrast to other MBD family members, MECP2 is X-linked and subject to X inactivation. MECP2 is dispensible in stem cells, but is essential for embryonic development. MECP2 gene mutations are the cause of most cases of Rett syndrome, a progressive neurologic developmental disorder and one of the most common causes of cognitive disability in females. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]

MECP2 Gene-Disease associations (from GenCC):

chromosome Xq28 duplication syndrome
Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
Rett syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P
severe neonatal-onset encephalopathy with microcephaly
Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
syndromic X-linked intellectual disability Lubs type
Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
atypical Rett syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked intellectual disability-psychosis-macroorchidism syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

MECP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant X-154029823-C-T is Benign according to our data. Variant chrX-154029823-C-T is described in ClinVar as Benign. ClinVar VariationId is 143276.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00204 (230/112529) while in subpopulation AMR AF = 0.00326 (35/10736). AF 95% confidence interval is 0.00241. There are 1 homozygotes in GnomAd4. There are 65 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High AC in GnomAd4 at 230 XL,Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MECP2	NM_001110792.2 link	c.*544G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000453960.7	NP_001104262.1
MECP2	NM_004992.4 link	c.*544G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000303391.11	NP_004983.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
MECP2	ENST00000453960.7 link	c.*544G>A	3_prime_UTR_variant	Exon 3 of 3	1	NM_001110792.2	ENSP00000395535.2
MECP2	ENST00000303391.11 link	c.*544G>A	3_prime_UTR_variant	Exon 4 of 4	1	NM_004992.4	ENSP00000301948.6
MECP2	ENST00000630151.3 link	c.*544G>A	3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000486089.2

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

230

AN:

112477

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00326

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00167

Gnomad SAS

AF:

0.00219

Gnomad FIN

AF:

0.000806

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00250

Gnomad OTH

AF:

0.00132

GnomAD4 exome

AF:

0.00240

AC:

AN:

35760

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

AN XY:

8152

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

1156

American (AMR)

AF:

0.00378

AC:

AN:

2649

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

737

East Asian (EAS)

AF:

0.000865

AC:

AN:

2313

South Asian (SAS)

AF:

0.00317

AC:

AN:

3472

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

1328

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00242

AC:

AN:

22280

Other (OTH)

AF:

0.00288

AC:

AN:

1739

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00204

AC:

230

AN:

112529

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

AN XY:

34691

show subpopulations

African (AFR)

AF:

0.00139

AC:

AN:

30981

American (AMR)

AF:

0.00326

AC:

AN:

10736

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00168

AC:

AN:

3577

South Asian (SAS)

AF:

0.00220

AC:

AN:

2732

European-Finnish (FIN)

AF:

0.000806

AC:

AN:

6204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00250

AC:

133

AN:

53208

Other (OTH)

AF:

0.00130

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000487

Hom.:

Bravo

AF:

0.00202

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autism, susceptibility to, X-linked 3

Uncertain:1

Nov 01, 2007

RettBASE

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:curation

- -

Rett syndrome

Benign:1

Aug 14, 2023

Centre for Population Genomics, CPG

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria.Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders to the ACMG/AMP Variant Interpretation Guidelines VCEP 2.0 , this variant is classified as benign. At least the following criteria are met: The allele frequency of this variant in at least one population in gnomAD is higher than the 0.03% threshold defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders VCEP 2.0 (BA1). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.28

(source)

DANN

Benign

0.66

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over